Structure-based design and synthesis of benzothiazole phosphonate analogues with inhibitors of human ABAD-Aβ for treatment of Alzheimer's disease.

ABSTRACT: Amyloid binding alcohol dehydrogenase, a mitochondrial protein, is a cofactor facilitating amyloid-β peptide (Aβ) induced cell stress. Antagonizing Aβ-ABAD interaction protects against aberrant mitochondrial and neuronal function and improves learning memory in the Alzheimer's disease mouse model. Therefore, it offers a potential target for Alzheimer's drug design, by identifying potential inhibitors of Aβ-ABAD interaction. 2D QSAR methods were applied to novel compounds with known IC(50) values, which formed a training set. A correlation analysis was carried out comparing the statistics of the measured IC(50) with predicted values. These selectivity-determining descriptors were interpreted graphically in terms of principle component analyses, which are highly informative for the lead opti

SUBMITTER: Valasani KR 

PROVIDER: S-EPMC3640359 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature